ABSTRACT
To assess the reporting quality of interventions aiming at promoting physical activity (PA) using a wearable activity tracker (WAT) in patients with inflammatory arthritis (IA) or hip/knee osteoarthritis (OA). A systematic search was performed in eight databases (including PubMed, Embase and Cochrane Library) for studies published between 2000 and 2022. Two reviewers independently selected studies and extracted data on study characteristics and the reporting of the PA intervention using a WAT using the Consensus on Exercise Reporting Template (CERT) (12 items) and Consolidated Standards of Reporting Trials (CONSORT) E-Health checklist (16 items). The reporting quality of each study was expressed as a percentage of reported items of the total CERT and CONSORT E-Health (50% or less = poor; 51-79% = moderate; and 80-100% = good reporting quality). Sixteen studies were included; three involved patients with IA and 13 with OA. Reporting quality was poor in 6/16 studies and moderate in 10/16 studies, according to the CERT and poor in 8/16 and moderate in 8/16 studies following the CONSORT E-Health checklist. Poorly reported checklist items included: the description of decision rule(s) for determining progression and the starting level, the number of adverse events and how adherence or fidelity was assessed. In clinical trials on PA interventions using a WAT in patients with IA or OA, the reporting quality of delivery process is moderate to poor. The poor reporting quality of the progression and tailoring of the PA programs makes replication difficult. Improvements in reporting quality are necessary.
Subject(s)
Osteoarthritis, Hip , Osteoarthritis, Knee , Humans , Fitness Trackers , Exercise , Osteoarthritis, Knee/therapy , Osteoarthritis, Hip/therapy , Lower ExtremityABSTRACT
BACKGROUND: Multiple sclerosis often leads to fatigue and changes in physical behavior (PB). Changes in PB are often assumed as a consequence of fatigue, but effects of interventions that aim to reduce fatigue by improving PB are not sufficient. Since the heterogeneous nature of MS related symptoms, levels of PB of fatigued patients at the start of interventions might vary substantially. Better understanding of the variability by identification of PB subtypes in fatigued patients may help to develop more effective personalized rehabilitation programs in the future. This study aimed to identify PB subtypes in fatigued patients with multiple sclerosis based on multidimensional PB outcome measures. METHODS: Baseline accelerometer (Actigraph) data, demographics and clinical characteristics of the TREFAMS-ACE participants (n = 212) were used for secondary analysis. All patients were ambulatory and diagnosed with severe fatigue based on a score of ≥35 on the fatigue subscale of the Checklist Individual Strength (CIS20r). Fifteen PB measures were used derived from 7 day measurements with an accelerometer. Principal component analysis was performed to define key outcome measures for PB and two-step cluster analysis was used to identify PB types. RESULTS: Analysis revealed five key outcome measures: percentage sedentary behavior, total time in prolonged moderate-to-vigorous physical activity, number of sedentary bouts, and two types of change scores between day parts (morning, afternoon and evening). Based on these outcomes three valid PB clusters were derived. CONCLUSIONS: Patients with severe MS-related fatigue show three distinct and homogeneous PB subtypes. These PB subtypes, based on a unique set of PB outcome measures, may offer an opportunity to design more individually-tailored interventions in rehabilitation. TRIAL REGISTRATION: Clinical trial registration no ISRCTN 82353628 , ISRCTN 69520623 and ISRCTN 58583714 .
Subject(s)
Behavior , Fatigue/psychology , Multiple Sclerosis/psychology , Accelerometry , Adolescent , Adult , Aged , Cluster Analysis , Cross-Sectional Studies , Fatigue/complications , Female , Humans , Male , Middle Aged , Multiple Sclerosis/complications , Principal Component Analysis , Young AdultABSTRACT
Background Computer-based cognitive rehabilitation is used to improve cognitive functioning after stroke. However, knowledge on adherence rates of stroke patients is limited. Objective To describe stroke patients' adherence with a brain training program using two frequencies of health professionals' supervision. Methods This study is part of a randomized controlled trial comparing the effect of the brain training program (600 min playtime with weekly supervision) with a passive intervention in patients with self-perceived cognitive impairments after stroke. Patients randomized to the control condition were offered the brain training after the trial and received supervision twice (vs weekly in intervention group). Adherence was determined using data from the study website. Logistic regression analyses were used to examine the impact of supervision on adherence. Results 53 patients allocated to the intervention group (group S8; 64% male, mean age 59) and 52 patients who were offered the intervention after the trial (group S2; 59% male, mean age 59) started the brain training. The median playtime was 562 min (range 63-1264) in group S8 vs. 193 min (range 27-2162) in group S2 (p < 0.001, Mann Whitney U). Conclusions The overall adherence of stroke patients with a brain training was low and there are some implications that systematic, regular interaction with a supervisor can increase training adherence of stroke patients with a restitution-focused intervention performed at home.
Subject(s)
Cognitive Dysfunction/rehabilitation , Cognitive Remediation/methods , Patient Compliance , Stroke Rehabilitation/methods , Stroke/therapy , Therapy, Computer-Assisted/methods , Aged , Cognitive Dysfunction/etiology , Female , Humans , Male , Middle Aged , Stroke/complicationsABSTRACT
Anaerobiospirillum succiniciproducens is known as an uncommon cause of diarrhea and bacteremia in humans, usually in immunocompromised hosts. We report four cases of A. succiniciproducens bloodstream infection in different hosts, including a previously healthy man. We describe clinical features, antibiotics susceptibility profile, treatment and outcomes. Strains were identified by 16S rRNA gene sequences which contributed to the extension of our MALDI-TOF MS database.
Subject(s)
Anaerobiospirillum/isolation & purification , Bacteremia/microbiology , Gram-Negative Bacterial Infections/microbiology , Adult , Aged, 80 and over , Anaerobiospirillum/chemistry , Anaerobiospirillum/drug effects , Anaerobiospirillum/genetics , Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/drug therapy , DNA, Bacterial/genetics , Female , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methodsABSTRACT
It is well known that the polar magnetic field is at its maximum during solar minima, and that the behaviour during this time acts as a strong predictor of the strength of the following solar cycle. This relationship relies on the action of differential rotation (the Omega effect) on the poloidal field, which generates the toroidal flux observed in sunspots and active regions. We measure the helicity flux into both the northern and the southern hemispheres using a model that takes account of the Omega effect, which we apply to data sets covering a total of 60 years. We find that the helicity flux offers a strong prediction of solar activity up to five years in advance of the next solar cycle. We also hazard an early guess as to the strength of Solar Cycle 25, which we believe will be of similar amplitude and strength to Cycle 24.
ABSTRACT
Wheelchair mobility performance is an important aspect in most wheelchair court sports, commonly measured with an indoor tracking system or wheelchair bound inertial sensors. Both methods provide key wheelchair mobility performance outcomes regarding speed. In this study, we compared speed profiles of both methods to gain insight into the level of agreement, for recommendations regarding future performance measurement. Data were obtained from 5 male highly trained wheelchair basketball players during match play. Players were equipped simultaneously with a tag on the footplate for the indoor tracking system (â¼8 Hz) and inertial sensors on both wheels and frame (199.8â¯Hz). Being part of a larger study on 3 vs 3 player game formats, data were collected in several matches with varying field sizes, but activity profiles closely resembled regular match play. Both systems provide similar outcomes regarding distance covered and average speed. Due to differences in sampling frequency and sensor location (reference point) on the wheelchair (for speed calculation), minor differences were revealed at low speeds (<2.5â¯m/s). Since both systems provide complementary features, a hybrid solution as proved feasible in this study, could possibly serve as the new gold standard for mobility performance measurement in wheelchair basketball or wheelchair court sports in general.
Subject(s)
Wheelchairs , Accelerometry/methods , Athletic Performance , Basketball , Exercise , Humans , Male , Young AdultABSTRACT
Quantitative assessment of an athlete׳s individual wheelchair mobility performance is one prerequisite needed to evaluate game performance, improve wheelchair settings and optimize training routines. Inertial Measurement Unit (IMU) based methods can be used to perform such quantitative assessment, providing a large number of kinematic data. The goal of this research was to reduce that large amount of data to a set of key features best describing wheelchair mobility performance in match play and present them in meaningful way for both scientists and athletes. To test the discriminative power, wheelchair mobility characteristics of athletes with different performance levels were compared. The wheelchair kinematics of 29 (inter-)national level athletes were measured during a match using three inertial sensors mounted on the wheelchair. Principal component analysis was used to reduce 22 kinematic outcomes to a set of six outcomes regarding linear and rotational movement; speed and acceleration; average and best performance. In addition, it was explored whether groups of athletes with known performance differences based on their impairment classification also differed with respect to these key outcomes using univariate general linear models. For all six key outcomes classification showed to be a significant factor (p<0.05). We composed a set of six key kinematic outcomes that accurately describe wheelchair mobility performance in match play. The key kinematic outcomes were displayed in an easy to interpret way, usable for athletes, coaches and scientists. This standardized representation enables comparison of different wheelchair sports regarding wheelchair mobility, but also evaluation at the level of an individual athlete. By this means, the tool could enhance further development of wheelchair sports in general.
Subject(s)
Athletic Performance/statistics & numerical data , Mechanical Phenomena , Statistics as Topic , Wheelchairs , Acceleration , Adult , Biomechanical Phenomena , Female , Humans , Male , MovementABSTRACT
OBJECTIVE: To assess the degree of fatigue in children and youth after traumatic and non-traumatic brain injury (TBI and NTBI) and related factors. METHOD: Follow-up study including patients with a hospital-based diagnosis of acquired brain injury (ABI), aged 4-20 years at onset and their parents. Parents and children (dependent on age) completed the Paediatric Quality of Life Inventory™ Multidimensional Fatigue Scale (PedsQL™ MFS), which measures general fatigue (GF), sleep/rest fatigue (SRF) and cognitive fatigue (CF). Additional assessments included the Child & Family Follow-up Survey (CFFS) and PedsQL™ 4.0 General Core Scales and sociodemographic and disease characteristics. RESULTS: Eighty-eight parents completed the PedsQL™ MFS 24-30 months after diagnosis, with 49/88 patients (56%) completing the child version. The median age of the patients was 11 years (interquartile range [IQR] = 7). There were 69 patients with TBI (16% moderate/severe TBI) and 19 patients with NTBI (16% moderate/severe NTBI). The median parent-reported and child-reported PedsQL™ MFS Total Scale Scores were 76.5 (SD = 16.4) and 78.5 (12.9), respectively (Spearman r = 0.450, p = 0.001). Apart from NTBI, increasing age and a single-parent household were significantly associated with more fatigue according to the parent-reported PedsQL™ MFS Total Score (and/or one or more sub-scale scores). CONCLUSION: Two years after onset, in particular, the parent-reported fatigue after NTBI was considerable. Moreover, older children and children from a single-parent household were found to have higher fatigue levels.
Subject(s)
Brain Injuries/complications , Fatigue/etiology , Parents/psychology , Adolescent , Age Factors , Brain Injuries/psychology , Child , Child, Preschool , Environment , Female , Follow-Up Studies , Health Surveys , Hospitals , Humans , Male , Mental Disorders/complications , Quality of Life/psychology , Young AdultABSTRACT
Cognitive impairment after stroke has a direct impact on daily functioning and quality of life (QoL) of patients and is associated with higher mortality and healthcare costs. The aim of this study was to determine the effect of a computer-based brain training programme on cognitive functioning, QoL and self-efficacy compared to a control condition in stroke patients. Stroke patients with self-perceived cognitive impairment were randomly allocated to the intervention or control group. The intervention consisted of an 8-week brain training programme (Lumosity Inc.®). The control group received general information about the brain weekly. Assessments consisted of a set of neuropsychological tests and questionnaires. In addition, adherence with trained computer tasks was recorded. No effect of the training was found on cognitive functioning, QoL or self-efficacy when compared to the control condition, except for very limited effects on working memory and speed. This study found very limited effects on neuropsychological tests that were closely related to trained computer tasks, but no transfers to other tests or self-perceived cognitive failures, QoL or self-efficacy. These findings warrant the need for further research into the value of computer-based brain training to improve cognitive functioning in the chronic phase after stroke.
Subject(s)
Cognition , Cognitive Dysfunction/rehabilitation , Quality of Life/psychology , Self Efficacy , Stroke Rehabilitation/methods , Stroke/psychology , Therapy, Computer-Assisted/methods , Aged , Attention , Cognitive Dysfunction/psychology , Female , Humans , Male , Memory, Short-Term , Middle Aged , Neuropsychological Tests , Self Concept , Single-Blind Method , Surveys and QuestionnairesABSTRACT
Knowledge of wheelchair kinematics during a match is prerequisite for performance improvement in wheelchair basketball. Unfortunately, no measurement system providing key kinematic outcomes proved to be reliable in competition. In this study, the reliability of estimated wheelchair kinematics based on a three inertial measurement unit (IMU) configuration was assessed in wheelchair basketball match-like conditions. Twenty participants performed a series of tests reflecting different motion aspects of wheelchair basketball. During the tests wheelchair kinematics were simultaneously measured using IMUs on wheels and frame, and a 24-camera optical motion analysis system serving as gold standard. Results showed only small deviations of the IMU method compared to the gold standard, once a newly developed skid correction algorithm was applied. Calculated Root Mean Square Errors (RMSE) showed good estimates for frame displacement (RMSE≤0.05 m) and speed (RMSE≤0.1m/s), except for three truly vigorous tests. Estimates of frame rotation in the horizontal plane (RMSE<3°) and rotational speed (RMSE<7°/s) were very accurate. Differences in calculated Instantaneous Rotation Centres (IRC) were small, but somewhat larger in tests performed at high speed (RMSE up to 0.19 m). Average test outcomes for linear speed (ICCs>0.90), rotational speed (ICC>0.99) and IRC (ICC> 0.90) showed high correlations between IMU data and gold standard. IMU based estimation of wheelchair kinematics provided reliable results, except for brief moments of wheel skidding in truly vigorous tests. The IMU method is believed to enable prospective research in wheelchair basketball match conditions and contribute to individual support of athletes in everyday sports practice.
Subject(s)
Wheelchairs , Acceleration , Accelerometry , Adult , Athletes , Basketball , Biomechanical Phenomena , Female , Humans , Male , Movement , Reproducibility of Results , Young AdultABSTRACT
AIM: To explore the effects of usage of the Nintendo Wii on physical, cognitive and social functioning in patients with acquired brain injury (ABI). METHODS: This multi-centre, observational proof-of-concept study included children, adolescents and young adults with ABI aged 6-29 years. A standardized, yet individually tailored 12-week intervention with the Nintendo Wii was delivered by trained instructors. The treatment goals were set on an individual basis and included targets regarding physical, mental and/or social functioning. Outcome assessments were done at baseline and after 12 weeks and included: the average number of minutes per week of recreational physical activity; the CAPE (Children's Assessment of Participation and Enjoyment); the ANT (Amsterdam Neuropsychological Tasks); the achievement of individual treatment goals (Goal Attainment Scaling); and quality-of-life (PedsQL; Pediatric Quality of Life Inventory). Statistical analyses included paired t-tests or Wilcoxon-Signed-Rank tests. RESULTS: Fifty patients were included (31 boys and 19 girls; mean age 17.1 years (SD = 4.4)), of whom 45 (90%) completed the study. Significant changes of the amount of physical activity, speed of information processing, attention, response inhibition and visual-motor coordination (p < 0.05) were seen after 12 weeks, whereas there were no differences in CAPE or PedsQL scores. Two-thirds of the patients reported an improvement of the main treatment goal. CONCLUSION: This study supports the potential benefits of gaming in children and youth with ABI.
Subject(s)
Achievement , Brain Injuries/rehabilitation , Psychomotor Performance , Therapy, Computer-Assisted/instrumentation , Video Games , Adolescent , Adult , Brain Injuries/physiopathology , Child , Female , Humans , Male , Motor Activity , Patient Compliance , Pilot Projects , Quality of Life , Therapy, Computer-Assisted/methods , Treatment Outcome , Young AdultABSTRACT
Objetivo: el objetivo del presente trabajo fue comparar, in vivo, la capacidad de sellado coronario de dos materiales de restauración provisoria, CAVIT y MD-Temp utilizados en combinación con un ionómero vítreo, luego de realizado el tratamiento endodóntico. Material y Métodos: se seleccionaron 40 pacientes que recibieron tratamiento endodóntico en la Clínica de la Carrera de Especialización en Endodoncia de la Escuela de Odontología de la Universidad del Salvador/Asociación Odontológica Argentina (USAL/AOA) lo que fueron asignados al azar a dos grupos de 20 (n=20) cada uno. En el Grupo 1) las cavidades de acceso fueron obturadas con CAVIT/Ionómero previa inserción de un disco de papel de 6mm de diámetro. En el Grupo 2) luego de la inserción del disco, se obturó con MD-Temp/Ionómero. A los 14 y 21 días los pacientes fueron citados para retirar los discos de papel. Los mismos se cultivaron para la detección de microorganismos anaerobios facultativos y anaerobios obligados. Los resultados fueron evaluados estadísticamente mediante el test exacto de Fisher y la prueba de chi cuadrado. El nivel de significación establecido fue de p>0,05. Resultados y conclusiones: las muestras basales no presentaron crecimiento bacteriano. En las muestras experimentales se aislaron Enterococcus faecalis, Lactobacilus spp., Streptococcus g viradas y levaduras. No se recuperaron anaerobios estrictos. A pesar de observase menor filtración en los casos obturados con CAVIT tanto a los 14 como a los 21 días no se observaron diferencias significativas entre ambos materiales, en los dos períodos evaluados (p>0,05) (AU)
Objective: The purpose of this study aimed to evaluate the coronal sealing ability of two temporary filling materials in vivo: CAVIT and MD-Temp, in combination with glass ionomer once the endodontics treatment was performed. Material and Methods: 40 patients were selected, all of which have received endodontic treatment at the Master in Endodontics Clinic of USAL/AOA. They were divided randomly in two groups of 20 (n=20) patients earch. After the insertion of 6 mm, paper disc in each of the patients of both groups, the coronal access cavities of Group 1 were obturated with CAVIT + glass ionomer; and those of Group 2, with MD Temp + glass ionomer. After 114 days and 21 days periods, all the patients have had the paper discs removed. Those paper-discss samples were sent to culture for facultative and force anaerobic microorganism. The results were statistically analyzed with chi squared and Fisher exact test. The significance level was p>0,05. Results and conclusions: Basal samples did not show bacterial growth. In experimental samples, Enterococcus faecalis, Lactobacillus spp., Streptococcus g viridians and levaduras were isolated. Force anaerobic microorganisms were not recovered. Though minor leakage was observed in cases obturated with CAVIT results reached both after the 14 days and 21 days periods, no statistically significant differences were observed amid both analyzed materials (p>0.05) (AU)
Subject(s)
Humans , Pit and Fissure Sealants/analysis , Glass Ionomer Cements/analysis , Bacteria, Anaerobic/isolation & purification , Root Canal Obturation/methods , Root Canal Preparation/methods , Dental Leakage/diagnosisABSTRACT
Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/beta-lactamase inhibitor combination currently available in 29 countries which may be a suitable option for treating intra-abdominal infections. the aim of this study was to identify the optimal dose and ratio between components of this formulation through an ex-vivo human pharmacodynamic model against Escherichia coli. Four volunteers were randomized to receive alternatively a single dose of AMX-SUL infused either over 30 min or 3h in the following ratios (g/g): 1/0.5; 1/1, 2/0.5 and 0/2. time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h post-dosing sera against E. coli ATCC 25922 (AMX MIC, 2 microg/ml; AMX-SUL MIC, 2 microg/ml) and E. coli ATCC 35218 (AMX MIC, 1024 microg/ml; AMX-SUL MIC, 4-8 microg/ml). AMX-SUL 1g/0.5 g infused over 30 min was only active at 0.5 h after dose, being inferior to both AMX-SUL 1g/1g and AMX-SUL 2g/0.5 g against E. coli ATCC 25922, for which the 2h post-dose serum proved active. When tested against E. coli ATCC 35218, AMX-SUL 1g/0.5 g and AMX-SUL 2g/0.5 g were active only at 0.5 h post-dose, whereas AMX-SUL 1g/1g showed bactericidal activity 0.5h post-dose and was able to inhibit bacterial growth 2 h post-dose. When infused over 3h, the antimicrobial activity of AMX-SUL was better than the 30-min infusion. Moreover, AMX-SUL 1g/1g was able to inhibit, and kill to some extent, the E. coli ATCC 25922 strain at 4h post-dose (i.e. 67% and 50% of a 6- and 8-h dosing interval, respectively). The present study suggests that 1g/1g is the best formulation for AMX-SUL against E. coli. The infusion over 3h optimizes its pharmacodynamic profile, as well as that of the 1g/0.5g combination. These findings encourage the performance of clinical trials to assess the efficacy of this combination, given as an extended infusion, in the treatment of community-acquired intra-abdominal infections.
Subject(s)
Amoxicillin/administration & dosage , Escherichia coli Infections/drug therapy , Sulbactam/administration & dosage , Adult , Amoxicillin/blood , Blood Bactericidal Activity , Cross-Over Studies , Drug Combinations , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Models, Biological , Single-Blind Method , Sulbactam/blood , Time FactorsABSTRACT
The characterization of the functional interactions between the metabotropic glutamate receptors (mGluR) and the dopaminergic (DR) receptors in the corticostriatal projections may provide a possible interpretation of synaptic events in the basal ganglia. It has been suggested that presynaptic D2-type receptor located on glutamatergic corticostriatal neurons regulates the release of glutamate. In a first approach we have studied the cellular distribution of the D4R and the mGluRs in cerebral cortex and striatum employing immunocytochemistry. D4R positive neurons were particularly numerous in medial prefrontal cortex mainly occupying layers II and III. An even distribution was found on small round-shaped neurons in the striatum. Group I mGluR1alpha-like immunoreactivity (mGluR1alpha-LI) was found in medial and deep layers of the cerebral cortex while group III mGluR4a labeled more superficial layers; group II mGluR2/3 signal was intense on fine fibers with a punctate appearance. In the striatum, mGluR1alpha and mGluR2/3 stained mainly fibers while mGluR4a labeled round shaped cell bodies. After lateral ventricular injection of colchicine, an axonal transport and firing activity blocker, D4R labeling significantly increased in cerebral cortex and decreased in the striatum. mGluR1alpha and mGluR4a signal decreased in cerebral cortex and only mGluR4a signal decreased in the striatum. These results support previous reports indicating a presynaptic localization of D4R in the striatum. In contrast, striatal mGluR1alpha appears to be a postsynaptic receptor probably synthesized in situ. Our results do not support the hypothesis of a colocalization of D4 receptor and one or more of the metabotropic glutamatergic receptors studied here.
Subject(s)
Cerebral Cortex/metabolism , Corpus Striatum/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Metabotropic Glutamate/metabolism , Animals , Colchicine/administration & dosage , Immunohistochemistry , Injections, Intraventricular , Male , Rats , Rats, Wistar , Receptors, Dopamine D4ABSTRACT
Lethal graft-versus-host disease (GVHD) can be induced after hematopoietic stem cell transplantation between major histocompatibility complex-matched murine strains expressing multiple minor histocompatibility antigen (miHA) differences. In the C57BL/6By (B6)-->C.B10-H2b/LiMcdJ (BALB.B) irradiation model, both CD4+ and CD8+ donor T cells can mediate lethal GVHD, whereas in the B6-->CXB-2/By (CXBE) model, in which the recipient expresses a subset of BALB.B miHA, only the CD8+ T cells are lethal. Phenotypic analysis of CD4+ T cells collected from the thoracic duct lymphocyte pool of recipient mice had indicated expansion of the donor T-cell receptor Vbeta6-9 families in BALB.B recipients, and only Vbeta7 and Vbeta9 populations in CXBE mice. CDR3-size spectratyping, used to further analyze these responses, revealed overlapping oligoclonal expansion of Vbeta4, Vbeta6-10, and Vbeta12-14 families in both BALB.B and CXBE recipients injected with host-presensitized B6 T cells. In addition, the B6-->BALB.B CD4+ T-cell response appeared to involve the recognition of unique BALB.B-specific miHA, indicated by additional skewing of Vbeta2 and Vbeta11 families. On the other hand, the B6-->CXBE strain combination exhibited unique skewing of the Vbeta16 and Vbeta18 families. Immunohistochemical staining of lingual epithelial sections from BALB.B recipients of naive B6 CD4+ T cells correlated with the involvement of several of the spectratype-skewed Vbeta families in GVHD lesions. Furthermore, magnetic cell separation techniques were used to positively select the spectratype-skewed Vbeta families from the donor B6 CD4+ T cells; the former were found to have significant GVHD potential upon transplantation into lethally irradiated BALB.B recipients. In contrast, mice that received transplants from the unskewed Vbeta families all survived with minimal symptoms of GVHD. Taken together, these results demonstrate that the expansion of particular Vbeta families, as identified by spectratype analysis, correlates with the induction and pathogenesis of lethal GVHD.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Graft vs Host Disease/immunology , Receptors, Antigen, T-Cell, alpha-beta/immunology , Animals , Cell Movement/immunology , Epithelial Cells/immunology , Epithelial Cells/pathology , Graft vs Host Disease/pathology , Mice , Minor Histocompatibility Antigens/immunology , Receptors, Antigen, T-Cell, alpha-beta/chemistryABSTRACT
We have identified a novel pre-TCR isoform that is structurally distinct from conventional pre-TCR complexes and whose TCR beta chains are inaccessible to anti-TCR beta antibodies. We term this pre-TCR isoform the MB (masked beta)-pre-TCR. Pre-T alpha (pT alpha) subunits of MB-pre-TCR complexes have a larger apparent mol. wt due to extensive modification with O:-linked carbohydrates; however, preventing addition of O-glycans does not restore antibody recognition of the TCR beta subunits of MB-pre-TCR complexes. Importantly, accessibility of TCR beta chains in MB-pre-TCR complexes is restored by filling in the 'missing' variable (V) domain of pT alpha with a V domain from TCR alpha. Moreover, the proportion of pre-TCR complexes in which the TCR beta subunits are accessible to anti-TCR beta antibody varies with the cellular context, suggesting that TCR beta accessibility is controlled by a trans-acting factor. The way in which this factor might control TCR beta accessibility as well as the physiologic relevance of TCR beta masking for pre-TCR function are discussed.
Subject(s)
Membrane Glycoproteins/deficiency , Membrane Glycoproteins/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/isolation & purification , Animals , Carbohydrate Sequence , Dimerization , Gene Transfer Techniques , Glycosylation , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Molecular , Molecular Sequence Data , Protein Isoforms/biosynthesis , Protein Isoforms/deficiency , Protein Isoforms/genetics , Protein Isoforms/isolation & purification , Protein Structure, Tertiary/genetics , Receptors, Antigen, T-Cell, alpha-beta/biosynthesis , Receptors, Antigen, T-Cell, alpha-beta/deficiency , Thymus Gland/cytology , Thymus Gland/immunology , Thymus Gland/metabolism , Tumor Cells, CulturedABSTRACT
Development of immature CD4-CD8- (double-negative) thymocytes to the CD4+CD8+ (double-positive) stage is linked to productive rearrangement of the TCRbeta locus by signals transduced through the pre-TCR. However, the mechanism whereby pre-TCR signaling is initiated remains unclear, in part due to the lack of an in vitro model system amenable to both biochemical and genetic analysis. In this study, we establish the thymic lymphoma Scid.adh as such a model system. Scid.adh responds to Ab engagement of surface IL-2Ra (TAC):CD3epsilon molecules (a signaling chimera that mimics pre-TCR signaling in vivo) by undergoing changes in gene expression observed following pre-TCR activation in normal thymocytes. These changes include down-regulation of CD25, recombinase-activating gene (RAG)-1, RAG-2, and pTalpha; and the up-regulation of TCRalpha germline transcripts. We term this complete set of changes in gene expression, in vitro maturation. Interestingly, Scid.adh undergoes only a subset of these changes in gene expression following Ab engagement of the pre-TCR. Our findings make two important points. First, because TAC:CD3epsilon stimulation of Scid.adh induces physiologically relevant changes in gene expression, Scid.adh is an excellent cellular system for investigating the molecular requirements for pre-TCR signaling. Second, Ab engagement of CD3epsilon signaling domains in isolation (TAC:CD3epsilon) promotes in vitro maturation of Scid.adh, whereas engagement of CD3epsilon molecules contained within the complete pre-TCR fails to do so. Our current working hypothesis is that CD3epsilon fails to promote in vitro maturation when in the context of an Ab-engaged pre-TCR because another pre-TCR subunit(s), possibly TCRzeta, qualitatively alters the CD3epsilon signal.
Subject(s)
Lymphoma, T-Cell/immunology , Lymphoma, T-Cell/pathology , Receptor-CD3 Complex, Antigen, T-Cell/physiology , Receptors, Antigen, T-Cell/physiology , Signal Transduction/immunology , Animals , Antibodies, Monoclonal/metabolism , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Membrane/immunology , Cell Membrane/metabolism , Mice , Mice, SCID , Receptor-CD3 Complex, Antigen, T-Cell/genetics , Receptor-CD3 Complex, Antigen, T-Cell/immunology , Receptor-CD3 Complex, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Interleukin-2/genetics , Receptors, Interleukin-2/immunology , Receptors, Interleukin-2/metabolism , Signal Transduction/genetics , Tumor Cells, CulturedABSTRACT
Beta-selection refers to a developmental checkpoint linking thymocyte survival to the outcome of antigen receptor gene rearrangement. Immature thymocytes that productively rear-range the gene segments of the TCRbeta locus undergo proliferative expansion and mature to the CD4(+)CD8(+)stage; those failing to do so die by apoptosis. How are these precursor cells alerted that TCRbeta rearrangement has been productive? While it is clear that this process involves signals transduced by a surrogate form of the TCR termed the pre-TCR, it remains unclear how pre-TCR signals are triggered. In this review, we will discuss the implications of recent experimental attempts to address this issue, as well as how pre-TCR activation is linked to the changes in gene expression that underlie thymocyte development.
Subject(s)
Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Animals , Cell Differentiation/immunology , Cell Lineage/immunology , Humans , Ligands , Lymphocyte ActivationABSTRACT
To evaluate the propulsive forces in front crawl arm swimming, derived from a three-dimensional kinematic analysis, these values were compared with mean drag forces. The propulsive forces during front crawl swimming using the arms only were calculated using three-dimensional kinematic analysis combined with lift and drag coefficients obtained in fluid laboratories. Since, for any constant swimming speed, the mean propulsive force should be equal to the mean drag force acting on the body of the swimmer, mean values of the calculated propulsive forces were compared with the mean drag forces obtained from measurements on a Measuring Active Drag (MAD) system. The two methods yielded comparable results, the mean difference between them being only 5% (2 N). We conclude that propulsive forces obtained from three-dimensional kinematic analysis provide realistic values. The calculation of the propulsive force appears to be rather sensitive to the point on the hand at which the velocity is estimated and less sensitive to the orientation of the hand.